Cohen I S, Falk R T, Mulrine N K
J Physiol. 1983 May;338:589-612. doi: 10.1113/jphysiol.1983.sp014691.
The actions of Ba2+ and Rb+, two blockers of background K+ conductance, were investigated. Recent studies performed on ungulate Purkinje fibres have suggested that the pace-maker current is an inward current activated by hyperpolarization. This hypothesis is based on the assumption that Ba2+ reduces the inwardly rectifying background K+ conductance without affecting the pace-maker current. Addition of 5 mM-BaCl2 to the bathing Tyrode solution decreases background K+ permeability and eliminates the reversal of the pace-maker current. The reversal reappears on return to Ba2+-free Tyrode solution. 5 mM-BaCl2 also reduces the time-dependent current at pace-maker potentials positive to about -95 mV in 4 mM-K+ Tyrode solution. The pace-maker current in Ba2+ Tyrode solution usually does not have an exponential time course, and often decays non-monotonically. It can take more than two minutes to reach a steady state. The fast initial component of membrane current, which is observed on hyperpolarizing in the pace-maker potential range in Purkinje fibres and which has been called the 'depletion current', is still present in Ba2+ Tyrode solution, but is reduced or eliminated if 10 mM-CsCl is added to the Ba2+ Tyrode solution. The addition of Cs+ is accompanied by an outward shift in membrane current in Ba2+ Tyrode solution. Ba2+ reduces the background K+ permeability in a dose-dependent manner. Addition of between 0.5 and 1 mM-BaCl2 achieves a maximum effect. Raising the amount of BaCl2 above this level reduces the time-dependent current even when no further effect on background permeability is observed. Rb+ substitution for K+ reduces the magnitude of the pace-maker current at potentials positive to -100 mV, eliminates the reversal of the pace-maker current, shifts the activation range to more negative potentials, and decreases the voltage dependence of pace-maker current kinetics. Rb+ addition to Tyrode solution has little effect on pace-maker current magnitude or time course positive to -90 mV, but does shift the reversal to more negative potentials. The available evidence suggests that the pace-maker current in Ba2+ Tyrode solution is an inward current activated by hyperpolarization. However, Ba2+ blocks an unknown fraction of the pace-maker current in a dose-dependent, and possibly voltage-dependent manner. Also, the presence of a slow component of pace-maker decay suggests that the standard Hodgkin-Huxley formalism for the analysis of pace-maker currents is inappropriate.
研究了两种背景钾离子电导阻滞剂钡离子（Ba2+）和铷离子（Rb+）的作用。最近对有蹄类动物浦肯野纤维进行的研究表明，起搏电流是一种由超极化激活的内向电流。这一假设基于这样的前提，即Ba2+降低内向整流背景钾离子电导而不影响起搏电流。向台氏液中添加5 mM的BaCl2可降低背景钾离子通透性，并消除起搏电流的反转。当回到无Ba2+的台氏液时，反转现象再次出现。在含4 mM钾离子的台氏液中，5 mM的BaCl2也会降低在高于约 -95 mV的起搏电位时的时间依赖性电流。在含Ba2+的台氏液中的起搏电流通常没有指数时间进程，且常呈非单调衰减。达到稳态可能需要两分钟以上。在浦肯野纤维的起搏电位范围内超极化时观察到的膜电流快速初始成分，即所谓的“耗竭电流”，在含Ba2+的台氏液中仍然存在，但如果向含Ba2+的台氏液中添加10 mM的CsCl，则该成分会减少或消除。添加Cs+会使含Ba2+的台氏液中的膜电流向外偏移。Ba2+以剂量依赖性方式降低背景钾离子通透性。添加0.5至1 mM的BaCl2可达到最大效果。即使未观察到对背景通透性有进一步影响，将BaCl2的量增加到该水平以上也会降低时间依赖性电流。用Rb+替代K+会降低在高于 -100 mV电位时起搏电流的幅度，消除起搏电流的反转，将激活范围移至更正的电位，并降低起搏电流动力学的电压依赖性。向台氏液中添加Rb+对高于 -90 mV时的起搏电流幅度或时间进程影响不大，但会将反转移至更负的电位。现有证据表明，含Ba2+的台氏液中的起搏电流是一种由超极化激活的内向电流。然而，Ba2+以剂量依赖性且可能是电压依赖性的方式阻断了未知比例的起搏电流。此外，起搏电流衰减存在缓慢成分，这表明用于分析起搏电流的标准霍奇金 - 赫胥黎形式体系并不适用。
